The objective of this NCRR Shared Instrument Grant application is to obtain funding to purchase a Thermo Electron Orbitrap XL-ETD mass spectrometer for the W.M. Keck Biomedical Mass Spectrometry Lab (MS Core) at the University of Virginia's School of Medicine. This instrument will be the foundation of high resolution/mass accuracy (HRMA) experiments in complex immunoprecipitation (IPs), biomarkers and post-translational modifications (PTMs). The goals of the University are to provide enhanced service in these areas, to provide higher capacity for these services, and to provide faster turnaround time for these projects. The Orbitrap X-ETD will meet these goals where existing instrumentation cannot. The MC Core is a heavily used facility providing mass spectrometry related expertise and services first to the UVA School of Medicine, then to the broader UVA community and finally to external institutions that do not have access to these services. This resource serves over 100 principle investigator labs per year in a wide variety of projects ranging from simple quality control (molecular weight measurements) to complex mixture analysis (biomarkers). At present the more complex experiments are run on a Thermo Electron LTQFT. This instrument is at full capacity and additionally the MS Core has only a 25% time interest. The remainder of this instrument's time is taken by projects for the proteomics section of the Cell Migration Consortium (U54 GM064346- 07 Horwitz -PI). Current projects in complex mixtures, biomarkers and PTMs utilize the LTQFT, but a 25% time interest does not provide enough resource for current projects and investigators either have to wait months to begin projects or be turned away. The new Orbitrap will provide an HRMA resource under primary control of the MS Core and allow investigators to pursue projects in a timely fashion. The MS Core has over 13 years experience in mass spectrometry and allied techniques. Our experience in consultation, both pre- and post-experiment, and our highly qualified staff make in-house mass spectrometry the preferred option for our investigators. With the new Orbitrap, our mission as a medium throughput facility will be fulfilled in several important areas that investigators are demanding more access to: 1) complex mixture analysis of IPs or cellular compartment purifications, 2) PTM analysis from complex mixtures (most requested - phosphorylation, ubiquitination, and methylation), and 3) biomarker analysis from complex clinical fluids. PUBLIC HEALTH RELEVANCE: The Thermo Electron Orbitrap XL-ETD mass spectrometer will be used to perform proteomics experiments that require high resolution and mass accuracy - complex mixtures, post-translational modifications, biomarkers, etc. These types of experimental studies range from fundamental cell control to cancer to infectious diseases. The NIH funding (and later descriptions) for the proposed projects clearly establishes these projects as research into public health issues that need a specific type of instrument operated by a highly qualified and successful mass spectrometry core. The W.M. Keck Biomedical Mass Spectrometry Lab at the University of Virginia's School of Medicine is a long established resource core with highly qualified personnel who have worked for over thirteen years with NIH funded investigators who have established research programs in biology and medicine. The purchase of this instrument is critical to their continued success.